Renin-Angiotensin System Inhibitor (RASi) Use and Atrasentan in IgAN: Post Hoc Analysis from the ALIGN Trial
Bibliographic record
Abstract
Background: Atrasentan, a highly selective ETA receptor antagonist, significantly reduced proteinuria vs placebo (pbo) in patients (pts) with IgAN in the ALIGN (NCT04573478) interim analysis. Atrasentan (VANRAFIA®) received US FDA accelerated approval for proteinuria reduction in adults with primary IgAN at risk of rapid disease progression. Given global variability in RASi regimens, a post hoc analysis assessed the ALIGN Week 36 primary endpoint data by baseline (BL) RASi class and dose. Methods: ALIGN is an ongoing, Phase III, randomized, double-blind study of atrasentan 0.75 mg/day vs pbo in adults with IgAN on stable, maximally tolerated RASi. Change from BL in 24-hour urine protein–creatinine ratio (24h-UPCR) at Week 36 was assessed by RASi class and by percentage of the maximum labeled dose (MLD) of RASi (≤50% or >50%) prescribed at BL. Results: Pts received two-thirds (69.0%) of MLD RASi on average. Of 270 pts, 54.4% received ≤50% MLD RASi and 41.1% received >50% MLD RASi. At BL, 71.1% and 27.4% of pts, respectively, were on an angiotensin II receptor blocker (ARB) and angiotensin-converting enzyme inhibitor (ACEi); 23 distinct ARBs and 10 distinct ACEis were prescribed. At Week 36, a 24h-UPCR reduction of 39.3% (95% CI 30.3, 47.0) was seen in the atrasentan arm for pts on ≤50% MLD RASi and a reduction of 37.5% (95% CI 27.4, 46.2) was seen in the atrasentan arm in pts on >50% MLD RASi (Figure). 24h-UPCR reductions of 36.8% (95% CI 28.9, 43.7) and 41.5% (95% CI 29.1, 51.7) were seen in the atrasentan arm for pts on ARB and ACEi, respectively. Conclusion: Atrasentan led to clinically meaningful proteinuria reduction regardless of BL RASi class (ARB or ACEi) and dose. These data support the potential for atrasentan to be seamlessly added onto a variety of existing RASi treatment and dose regimens. The results add to the available data for atrasentan, which has the potential to be a foundational therapy in IgAN. Funding: Commercial Support - Novartis
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".